[3] Zagel began his career as an assistant state's attorney in Cook County, Illinois, from 1965 until 1969, where he helped compile the case against mass murderer Richard Speck.

[3] In 1977, Zagel became executive director of the Illinois Law Enforcement Commission, a post he held until 1979.

[1][6] Zagel presided over many notable and high-profile trials, including the Jesse Webster case and the "Family Secrets" trial that ended in 2007, where he convicted numerous mobsters, such as Joseph Lombardo and Frank Calabrese Sr.[2][7] In April 2009, it was announced that Zagel would preside over the federal corruption trial of former Illinois Governor Rod Blagojevich and his brother, Robert Blagojevich.

He was retried in June 2011, with Zagel presiding, and the jury returned a guilty verdict on 17 of the remaining counts, including those pertaining to the Obama Senate seat.

[2] Zagel was described as a "Renaissance man" with a wide variety of interests outside of the courtroom; fellow judge Manish S. Shah told The New York Times that Zagel "could quote Ludwig Wittgenstein and Groucho Marx with an easy charm".

[9] In 2002, he published a novel titled Money to Burn,[10] a fictional thriller about a plot to rob the Federal Reserve Bank.

Zagel and his first wife, Chicago Tribune investigative reporter Pam Zekman, divorced in 1975.